Discovery and structure-activity relationship of coumarin derivatives as TNF-α inhibitors

Article abstract of DOI:10.1016/j.bmcl.2004.03.022

The discovery and structure-activity relationship of a novel series of coumarin-based TNF-α inhibitors is described. Starting from the initial lead 1a, various derivatives were prepared surrounding the coumarin core structure to optimize the in vitro inhibitory activity of TNF-α production by human peripheral blood mononuclear cells (hPBMC), stimulated by bacterial lipopolysaccharide (LPS). Selected compounds also demonstrated in vivo inhibition of TNF-α production in rats.